title: High-dose daptomycin therapy for left-sided infective endocarditis: a prospective study from the international collaboration on endocarditis.
abstract: The use of daptomycin in Gram-positive left-sided infective endocarditis (IE) has significantly increased. The purpose of this study was to assess the influence of high-dose daptomycin on the outcome of left-sided IE due to Gram-positive pathogens. This was a prospective cohort study based on 1,112 cases from the International Collaboration on Endocarditis (ICE)-Plus database and the ICE-Daptomycin Substudy database from 2008 to 2010. Among patients with left-sided IE due to Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus faecalis, we compared those treated with daptomycin (cohort A) to those treated with standard-of-care (SOC) antibiotics (cohort B). The primary outcome was in-hospital mortality. Time to clearance of bacteremia, 6-month mortality, and adverse events (AEs) ascribable to daptomycin were also assessed. There were 29 and 149 patients included in cohort A and cohort B, respectively. Baseline comorbidities did not differ between the two cohorts, except for a significantly higher prevalence of diabetes and previous episodes of IE among patients treated with daptomycin. The median daptomycin dose was 9.2 mg/kg of body weight/day. Two-thirds of the patients treated with daptomycin had failed a previous antibiotic regimen. In-hospital and 6-month mortalities were similar in the two cohorts. In cohort A, median time to clearance of methicillin-resistant S. aureus (MRSA) bacteremia was 1.0 day, irrespective of daptomycin dose, representing a significantly faster bacteremia clearance compared to SOC (1.0 versus 5.0 days; P < 0.01). Regimens with higher daptomycin doses were not associated with increased incidence of AEs. In conclusion, higher-dose daptomycin may be an effective and safe alternative to SOC in the treatment of left-sided IE due to common Gram-positive pathogens.
authors.affiliation: Department of Clinical Science, University of Milan, Luigi Sacco Hospital, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Carugati
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Bayer
authors.forename: Josè M
authors.initials: JM
authors.lastname: Miró
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Park
authors.forename: Armenio C
authors.initials: AC
authors.lastname: Guimarães
authors.forename: Athanasios
authors.initials: A
authors.lastname: Skoutelis
authors.forename: Claudio Q
authors.initials: CQ
authors.lastname: Fortes
authors.forename: Emanuele
authors.initials: E
authors.lastname: Durante-Mangoni
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Hannan
authors.forename: Francisco
authors.initials: F
authors.lastname: Nacinovich
authors.forename: Nuria
authors.initials: N
authors.lastname: Fernández-Hidalgo
authors.forename: Paolo
authors.initials: P
authors.lastname: Grossi
authors.forename: Ru-San
authors.initials: RS
authors.lastname: Tan
authors.forename: Thomas
authors.initials: T
authors.lastname: Holland
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Corey
authors.forename: Vivian H
authors.initials: VH
authors.lastname: Chu
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017576:Daptomycin / Q000627:therapeutic use*; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D013293:Enterococcus faecalis / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013211:Staphylococcus aureus / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin